Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation.

Abstract

BACKGROUND:

Recombinant human growth hormone (rhGH) is licensed for short stature associated with growth hormone deficiency (GHD), Turner syndrome (TS), Prader-Willi syndrome (PWS), chronic renal insufficiency (CRI), short stature homeobox-containing gene deficiency (SHOX-D) and being born small for gestational age (SGA).

OBJECTIVES:

To assess the clinical effectiveness and cost-effectiveness of rhGH compared with treatment strategies without rhGH for children with GHD, TS, PWS, CRI, SHOX-D and those born SGA.

DATA SOURCES:

The systematic review used a priori methods. Key databases were searched (e.g. MEDLINE, EMBASE, NHS Economic Evaluation Database and eight others) for relevant studies from their inception to June 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK.

STUDY SELECTION:

Two reviewers assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers, and screened them against inclusion criteria.

STUDY APPRAISAL:

Data from included studies were extracted by one reviewer and checked by a second. Quality of included studies was assessed using standard criteria, applied by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through a narrative review.

RESULTS:

Twenty-eight randomised controlled trials (RCTs) in 34 publications were included in the systematic review. GHD: Children in the rhGH group grew 2.7 cm/year faster than untreated children and had a statistically significantly higher height standard deviation score (HtSDS) after 1 year: -2.3 ± 0.45 versus -2.8 ± 0.45. TS: In one study, treated girls grew 9.3 cm more than untreated girls. In a study of younger children, the difference was 7.6 cm after 2 years. HtSDS values were statistically significantly higher in treated girls. PWS: Infants receiving rhGH for 1 year grew significantly taller (6.2 cm more) than those untreated. Two studies reported a statistically significant difference in HtSDS in favour of rhGH. CRI: rhGH-treated children in a 1-year study grew an average of 3.6 cm more than untreated children. HtSDS was statistically significantly higher in treated children in two studies. SGA: Criteria were amended to include children of 3+ years with no catch-up growth, with no reference to mid-parental height. Only one of the RCTs used the licensed dose; the others used higher doses. Adult height (AH) was approximately 4 cm higher in rhGH-treated patients in the one study to report this outcome, and AH-gain SDS was also statistically significantly higher in this group. Mean HtSDS was higher in treated than untreated patients in four other studies (significant in two). SHOX-D: After 2 years' treatment, children were approximately 6 cm taller than the control group and HtSDS was statistically significantly higher in treated children. The incremental cost per quality adjusted life-year (QALY) estimates of rhGH compared with no treatment were: 23,196 pounds for GHD, 39,460 pounds for TS, 135,311 pounds for PWS, 39,273 pounds for CRI, 33,079 pounds for SGA and 40,531 pounds for SHOX-D. The probability of treatment of each of the conditions being cost-effective at 30,000 pounds was: 95% for GHD, 19% for TS, 1% for PWS, 16% for CRI, 38% for SGA and 15% for SHOX-D.

LIMITATIONS:

Generally poorly reported studies, some of short duration.

CONCLUSIONS:

Statistically significantly larger HtSDS values were reported for rhGH-treated children with GHD, TS, PWS, CRI, SGA and SHOX-D. rhGH-treated children with PWS also showed statistically significant improvements in body composition measures. Only treatment of GHD would be considered cost-effective at a willingness-to-pay threshold of 20,000 to 30,000 pounds per QALY gained. This analysis suggests future research should include studies of longer than 2 years reporting near-final height or final adult height.

• Authors: A Takeda, K Cooper, A Bird, L Baxter, G K Frampton, E Gospodarevskaya, K Welch, J Bryant
• Journal: Health technology assessment (Winchester, England) (Health Technol Assess) Vol. 14 Issue 42 Pg. 1-209, iii-iv (Sep 2010) ISSN: 2046-4924 [Electronic] England
• PMID: 20849734 (Publication Type: Journal Article, Review, Systematic Review)

Chemical References

• Biomarkers
• Human Growth Hormone

Topics

• Biomarkers
• Body Composition
• Cost-Benefit Analysis
• Dwarfism, Pituitary (drug therapy, economics)
• Growth Disorders (drug therapy, economics)
• Human Growth Hormone (economics, therapeutic use)
• Humans
• Incidence
• Linear Models
• Models, Economic
• Prevalence
• Prognosis
• Quality Assurance, Health Care
• Quality of Life (psychology)
• Quality-Adjusted Life Years
• United States